U.S. patent number 11,385,209 [Application Number 16/643,627] was granted by the patent office on 2022-07-12 for chromatography cartridge and method of production thereof.
This patent grant is currently assigned to Biotage AB. The grantee listed for this patent is Biotage AB. Invention is credited to Juha Esala, Andreas Norlen, Per Normann.
United States Patent |
11,385,209 |
Esala , et al. |
July 12, 2022 |
Chromatography cartridge and method of production thereof
Abstract
The present invention relates to a pre-packed chromatography
cartridge (10) suitable for flash chromatography. The
chromatography cartridge (10) comprises a barrel (20) having one
end sealed with a cap (40), a thread (23) arranged on the outer
cylindrical surface of the barrel (20) and engaged to a mating
thread (43) on the inner cylindrical surface of the cap (40). The
barrel is provided with at least one protrusion (24) arranged on
the outer cylindrical surface and below the thread (23) in the
direction from the end sealed by the cap (40). The protrusion (24)
extends essentially radially outwards from the outer cylindrical
surface of the barrel (20). The cap (40) is provided with a
cylindrical flange (44) arranged below the thread (43) of the cap
(40). A locking member (46) is arranged on the flange (44) and
extends essentially radially inwards from the inner cylindrical
surface of the flange (44). Together with the protrusion (24) of
the barrel (20), the locking member (46) forms a mechanical
connection that secures the cap (40) such that it cannot be
unscrewed from the barrel (20).
Inventors: |
Esala; Juha (Vattholma,
SE), Norlen; Andreas (Bergshamra, SE),
Normann; Per (Uppsala, SE) |
Applicant: |
Name |
City |
State |
Country |
Type |
Biotage AB |
Uppsala |
N/A |
SE |
|
|
Assignee: |
Biotage AB (Uppsala,
SE)
|
Family
ID: |
1000006426035 |
Appl.
No.: |
16/643,627 |
Filed: |
August 29, 2018 |
PCT
Filed: |
August 29, 2018 |
PCT No.: |
PCT/EP2018/073215 |
371(c)(1),(2),(4) Date: |
March 02, 2020 |
PCT
Pub. No.: |
WO2019/043050 |
PCT
Pub. Date: |
March 07, 2019 |
Prior Publication Data
|
|
|
|
Document
Identifier |
Publication Date |
|
US 20200400624 A1 |
Dec 24, 2020 |
|
Foreign Application Priority Data
|
|
|
|
|
Sep 1, 2017 [EP] |
|
|
17189076 |
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
G01N
30/6091 (20130101); G01N 30/6004 (20130101); B01D
15/165 (20130101); G01N 30/6052 (20130101); G01N
2030/027 (20130101) |
Current International
Class: |
B01D
15/16 (20060101); G01N 30/60 (20060101); G01N
30/02 (20060101) |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
International Search Report PCT/ISA/210 for International
Application No. PCT/EP2018/073215 dated Nov. 20, 2018. cited by
applicant.
|
Primary Examiner: Lebron; Benjamin L
Attorney, Agent or Firm: Harness, Dickey & Pierce,
P.L.C.
Claims
The invention claimed is:
1. A chromatography cartridge comprising: a barrel having at least
one end sealed with a cap,.sub.-- the barrel comprising a thread
arranged on the outer cylindrical surface of the barrel and the cap
comprising a mating thread on an inner cylindrical surface of the
cap, the cap having an inlet end and an open end, wherein: the
barrel comprises at least one protrusion arranged on the outer
cylindrical surface and below the thread of the barrel in the
direction from the end sealed by the cap, the protrusion extending
essentially radially outwards from the outer cylindrical surface of
the barrel; and wherein the cap comprises a cylindrical flange
arranged below the thread of the cap in the direction from the
inlet end of the cap, the flange accommodating the protrusion, and
at least one locking member provided on the inner cylindrical
surface of the flange and extending essentially radially inwards;
and wherein the cartridge comprises a mechanical connection formed
by the locking member of the cap and the protrusion of the barrel,
wherein the locking member is an indent in the flange of the
cap.
2. The chromatography cartridge according to claim 1, wherein the
locking member is a local deformation of the flange and the local
deformation has been provided to the flange after the cap has been
mounted onto the barrel.
3. The chromatography cartridge according to claim 1, wherein at
least a portion of the indent is plastically deformed.
4. The chromatography cartridge according to claim 3, wherein the
indent has been formed by a punching operation resulting in the at
least partly plastically deformed indent.
5. The chromatography cartridge according to claim 1, wherein an
overlap in the radial direction between the protrusion and the
indent exceeds one third of the length that the protrusion extends
from the outer surface of the barrel.
6. The chromatography cartridge according to claim 5, wherein the
indent is arranged after the protrusion in the screw direction and
abuts the protrusion.
7. The chromatography cartridge according to claim 2, wherein the
locking member is a melted structure in the flange of the cap,
wherein the melted structure has been formed by localized melting
of a portion of the flange.
8. The chromatography cartridge according to claim 1, wherein the
mechanical connection formed by the protrusion and the locking
member is arranged to withstand a first predetermined torque and to
break at a second predetermined torque, the first and second
predetermined torque asserted in the direction opposite to the
screw direction.
9. The chromatography cartridge according to claim 8, wherein the
first predetermined torque corresponds to a torque achievable by a
user using her hands manually unscrewing the cap and the second
predetermined torque is in the range 1.3-2 times the first
predetermined torque.
10. The chromatography cartridge according to claim 1, wherein a
plurality of protrusions and locking members pairs are provided on
the barrel and the flange respectively.
11. A method of manufacturing a closed chromatography cartridge
according to claim 1, the cartridge comprising at least a barrel, a
cap and chromatography media, the cap adapted to be screwed onto
the barrel in a predetermined screw direction, the barrel
comprising at least one protrusion arranged on the outer
cylindrical surface of the barrel and the cap provided with a
flange that is adapted to accommodate the protrusion in a mounted
position on the barrel, the method comprising the steps of:
providing a barrel packed with at least chromatography media;
positioning the barrel in a punching equipment comprising at least
one punch and aligning the protrusion of the barrel so that the
punch is positioned a predetermined distances after the protrusion
in the screw direction; applying the cap to the top of the barrel;
screwing the cap and/or the barrel to a predetermined position
and/or with a predetermined torque; punching the flange of the cap
to produce at least one indent.
12. The method according to claim 11, wherein the positioning step
comprises mating alignment means provided on the barrel with
corresponding alignment means provided on a support structure of
the punching equipment.
13. The method according to claim 12, wherein the barrel is
provided with a plurality of protrusions, the method further
comprising to, after a first punching step at a first protrusion,
rotating the barrel and aligning a second protrusion with regards
to the punch and repeating the punching step.
14. The method according to claim 11, wherein the punching step
comprises punching with a plurality of punches each producing an
indent, and wherein the punching with the plurality of punches is
simultaneous in order to have a balanced operation.
15. The method according to claim 11, wherein the punching step
produces an at least a partly plastically deformed indent.
Description
This application is a national phase under 35 U.S.C. .sctn. 371 of
PCT International Application No. PCT/EP2018/073215, which has an
International filing date of Aug. 29, 2018, which claims priority
to European Patent Application No. 171890767, filed Sep. 1, 2017,
the entire contents of each of which are hereby incorporated by
reference.
FIELD OF THE INVENTION
The present invention relates to chromatography, and more
particularly to a pre-packed chromatography cartridge suitable for
high pressure as well as a method for the production of such a
pre-packed cartridge.
BACKGROUND OF THE INVENTION
Chromatography is a chemical separation technique utilizing the
fact that substances to be separated are distributed in different
ways between a stationary phase and a mobile phase. The stationary
phase, or separation medium, which typically is an adsorption
medium, an ion-exchanger material, a gel or a surface-modified
solid material, is usually packed in a column. Different components
in a sample applied to the top of the medium bed will migrate
through the column at different rates depending, e.g., on their
size and degree of attraction to the stationary phase when the
liquid passes through the column. Liquid chromatography is
extensively used for chemical analysis as well as for preparative
separations in research and industry.
In traditional chromatography, the liquid or solvent passes through
the column by gravity. The rate at which the liquid passes through
the column is therefore relatively slow. To speed up the rate of
the chromatography process, the liquid is forced through the column
by the application of a positive pressure. This may be accomplished
by pumping the liquid through the column, such as in HPLC (high
performance liquid chromatography), or by the application of a
positive air-pressure, such as in flash chromatography. Modern
flash chromatography typically uses plastic pre-packed disposable
columns or cartridges and in most variants the liquid is pumped
through the column or cartridge.
The disposable cartridges used for flash chromatography are usually
manufactured with economy in mind, which involves manufacturing the
cartridges of inexpensive plastics and designing the columns to be
easily assembled by filling the body of the column with the desired
packing, usually with frit plugs on each end of the packing to hold
the packing in place, and then closing the open end or ends of the
columns by end pieces or caps, e.g. by screwing or snapping them to
the column ends. The end pieces may also be glued or welded to the
column, for example by spin welding or heat plate welding. The
modern flash chromatography puts high demands on the cartridges
being leak tight and that this property is maintained throughout
the process without requiring a delicate handling. Considerable
efforts have been made to provide disposable cartridges that are
suited for high volume manufacturing at a reasonable cost and yet
are sufficiently rigid and leakproof.
The majority of cartridges for flash chromatography are provided to
the end user as a closed pre-packed product. However for certain
applications it is desirable to load the sample directly into the
column or modify the column. For these purposes so called open
cartridges are provided. Typically such cartridges are provided
with a screw or snap cap. The demand for open cartridges forces the
manufacturer to manufacture and store two separate types of
cartridges, which is undesirable from an economic standpoint both
from the perspective of handling and storing and that multiple
moulds are needed for the production of the cartridges.
A further requirement of today is that the cartridges should be
possible to re-cycle without costly measures. Re-cycling typically
requires separating the packed material, at this staged typically
containing residue liquids, from the plastic cartridge. The
permanently closed cartridges, which are most common, are not well
suited for efficient re-cycling.
SUMMARY OF THE INVENTION
The object of the invention is to provide a disposable cartridge
for flash chromatography that overcomes the drawbacks of prior art
cartridges and manufacturing techniques. This is achieved by the
cartridge as defined in claim 1, the barrel as defined in claim 12,
the kit as defined in claim 13, and the method of manufacturing the
cartridge as defined in claim 14.
The chromatography cartridge according to the invention comprises a
barrel having at least one end sealed with a cap, a thread arranged
on the outer cylindrical surface of the barrel and engaged to a
mating thread on the inner cylindrical surface of the cap being
mounted onto the barrel. The barrel is provided with at least one
protrusion arranged on the outer cylindrical surface and below the
thread in the direction from the end sealed by the cap. The
protrusion extends essentially radially outwards from the outer
cylindrical surface of the barrel. The cap is provided with a
cylindrical flange arranged below the thread of the cap in the
direction from the inlet end. The flange should accommodate the
protrusion or protrusions. At least one locking member is arranged
on the flange and extends essentially radially inwards from the
inner cylindrical surface of the flange. Together with the
protrusion of the barrel, the locking member forms a mechanical
connection that secures that the cap can not be unscrewed from the
barrel, at least not with a force/torque that is achievable by a
user using her bare hands.
According to one aspect of the invention the locking member is a
local deformation of the flange and the local deformation has been
provided to the flange after the cap has been mounted onto the
barrel. The local deformation may for example be in the form of an
indent which is a result of a punching operation onto the flange or
a melted structure being a result of a local melting of the
flange.
According to another aspect of the invention, the indent may, as a
result of the punching operation, be at least partially plastically
deformed. Preferably there is an overlap in the radial direction
between the protrusion and the indent that exceeds half the length
that the protrusion extends from the outer surface of the barrel.
Preferably the indent is arranged after the protrusion in the screw
direction and abuts the protrusion.
According to one aspect of the invention the mechanical connection
formed by the protrusion and the locking member is arranged to
withstand a first predetermined torque and to break at a second
predetermined torque, the first and second predetermined torque
asserted in the direction opposite to the screw direction, the
direction of unscrewing the cap from the barrel. The first
predetermined torque should relate to a torque achievable by a user
using her bare hands to unscrew the cap and the second
predetermined torque should be in the range 1.3-2 times the first
predetermined torque. Hence, it should with a margin be ensured
that a user without the aid of a tool or machinery can not open the
cartridge. Yet it should be possible to, with suitable tool
providing a lever or machinery, open the cartridge without complete
demolition of the cartridge.
According to a further aspect a plurality of pairs of protrusions
and locking members are provided on the barrel and the flange,
respectively.
The barrel for a chromatography cartridge according to the
invention, the barrel has at least one end arranged to be sealed
with a cap, a thread arranged on the outer surface of the barrel
and adapted to be engaged with a corresponding thread on the inner
cylindrical surface of a cap. The barrel is provided with at least
one protrusion arranged on the outer cylindrical surface and below
the thread in the direction from the end adapted for being sealed
by a cap. The protrusion extends essentially radially outwards from
the outer cylindrical surface of the barrel and is adapted to form
a mechanical connection with a locking member that extends
essentially radially inwards from an inner cylindrical surface of a
flange of the cap.
The method according to the invention of manufacturing a pre-packed
chromatography cartridge comprising a barrel and a cap according to
the above described, comprises the steps of: providing a barrel
with at least chromatography media; positioning the barrel in a
punching equipment comprising at least one punch and aligning the
protrusion of the barrel so that the punch is positioned a
predetermined distances after the protrusion in the screw
direction; applying the cap to the top of the barrel; screwing the
cap to a predetermined position and/or with a predetermined torque;
punching the flange of the cap to produce at least one indent, and
so that the indent after the punching operation will abut the
protrusion.
According to one aspect, the method of the invention comprises, in
the positioning step, mating alignment means provided on the barrel
with corresponding alignment means provided on a support structure
of the punching equipment.
According to one aspect of the invention of invention the punch
depth/force of the punch is selected to give an indent that is at
least partly plastically deformed.
According to another aspect the punching step comprises punching
with a plurality of punches, each producing an indent, and wherein
the punching with the plurality of punches is simultaneous in order
to have a balanced operation.
Thanks to the invention a cartridge is provided wherein the same
barrel can be used for both open and closed cartridges. The closed
cartridges are locked as a last step, or one of the last steps, in
the assembling process and in a manner that is cost effective and
gentle to the media etc. in the packed cartridge.
One advantage of the invention is that the cartridge can be
designed not to be opened by accident or by mistake or even if a
user tries to open the cartridge by normal means. This ensures that
the content of the cartridge is intact and that the chromatograph
equipment is not damaged by incorrect use or that invalid or
questionable results are produced. At the same time the cartridge
can be opened in a controlled way if correct tools are used, for
example for separating the media in the interior from the plastic
parts for recycling purposes.
The method according to the invention makes it possible to provide
the locking function in a way that is cost effective and does not
cause any damage to the media or the other internal parts. If a
plurality of punches are used and in a simultaneous action there is
no need to realign the cartridge between punches and less resulting
force is experienced by the cartridge which means less risk of
affecting the carefully packed media bed.
In the following, the invention will be described in more detail,
by way of example only, with regard to non-limiting embodiments
thereof, reference being made to the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 (a) is a schematic exploded perspective view, (b) is a
perspective view of a sealed cartridge, and (c) a cross-sectional
view, of an embodiment of the chromatographic cartridge according
to the present invention;
FIG. 2 is a flowchart of the method according to the invention;
and
FIG. 3 a-b are schematic illustrations of one of the steps of the
method according to the invention.
DETAILED DESCRIPTION
Terms such as "top", "bottom", upper", lower", etc are used merely
with reference to the geometry of the embodiment of the invention
shown in the drawings and are not intended to limit the invention
in any manner.
As described in the background section flash chromatography
cartridges are typically distributed in a closed pre-packed
configuration, although also open cartridges are provided. Open
typically meaning that the end user can open a top enclosure of the
cartridge and after preparation close the cartridge again. A
pre-packed cartridge is typically produced by closing the bottom of
the barrel with a bottom cap, mount the interior parts and close
with a top cap. Most parts are typically pre-fabricated in
automated moulding processes. The production can very simplified be
described as a two stage process, wherein in the first stage the
plastic parts are fabricated and in the second stage the cartridge
is packed and sealed. The second stage is typically more adaptable
to various end applications, customer demands etc.
The cartridge 10 according to the present invention is
schematically depicted in FIGS. 1a-c. FIG. 1a is an exploded view,
1b a close up of the inlet portion of the cartridge 10 and 1c a
cross-sectional view of the inlet portion of the cartridge 10. The
cartridge 10 comprises a barrel 20, typically a cylindrical plastic
tube, provided with an outlet end piece 30 arranged to close the
barrel 20 and provide an outlet 31 in one in end. A cap 40 is
provided with an inlet 41 on its inlet end 45 and arranged at the
other end, its open end 47, on the inlet end of the barrel 20. Also
the cap 40 and end piece 30 are typically of a plastic material,
commonly the same plastic material as the barrel 20. Alternatively
the outlet end piece 30 is fully integrated in the barrel 20. As
appreciated by the skilled person a cartridge for flash
chromatography comprises a number of other functional parts
comprised within the cartridge, such as inlet and outlet frits,
chromatography medium e.g. silica as well as various support
structures. For clarity, these features are not shown. Similarly
the cartridge may be provided with support or mounting structures
for mounting the cartridge onto or into the chromatography
apparatus. Also for clarity, such external structures are not shown
or discussed.
According to the invention the inlet end of the barrel 20 that will
engage with the cap 40, is provided with a thread 23 on its outer
cylindrical surface and adjacent to the inlet end of the barrel 20.
The barrel 20 and the cap 40 are provided with matching sealing
means (not shown) to seal the cartridge to typically a
predetermined pressure specification. The thread 23 is preferably a
normal right-hand thread giving a clockwise screw direction
indicated with an arrow in FIG. 1a. Below the thread 23 in the
direction from the inlet end of the barrel 20, is at least one
protrusion 24 provided. The protrusion 24 extents from the outer
surface of the barrel 20 in an essentially outwards radial
direction, preferably with a height of 0.5-5 mm from the surface of
the barrel 20. The protrusion 24 of the barrel 20 is adapted to
interact with a post-fabricated locking member 46 of the cap 40 to
form a mechanical connection. The mechanical connection will after
the final assembly of the cartridge, then the locking member 46 of
the cap 40 has been provided, prevent the cap 40 from being
unscrewed. The locking member 46 may for example be an indent, a
melted structure in the flange 44 or added material to the flange
44, which represent different embodiments of the invention. In the
following an indent is used as an illustrative example. As
appreciated by the skilled person the requirements and
characteristics are relevant also for other types of locking
members.
According to one embodiment the locking member 46 is a melted
structure that has been provided to the cap 40 during the final
assembly by localised melting.
As will be further described below, the protrusion 24 should
interact with a locking member in the cap 40 to provide a locking
function of the cap 40 to the barrel 20. The design of the
protrusion 24 can be varied relatively freely as long as the
interaction with the locking member of the cap 40 is such that a
secure locking is ensured. According to one embodiment the side of
the protrusion that faces a direction that is opposite the screw
direction is essentially perpendicular to the outer surface of the
barrel 20. According to one embodiment the protrusion comprises a
flat surface facing a direction that is opposite the screw
direction, and forms an angle to the outer surface of the barrel 20
that is less than 90 degrees, so as to form a hooked shaped
design.
Sides of the protrusion 24 may be curved or sloped towards the
cylindrical surface of the barrel 20. In particular the side of the
protrusion 24 facing the screw direction may be sloped to increase
the stability of the protrusion.
The cap 40 has a closed end provided with the inlet 41 forming the
inlet part of the cartridge 10 and an open end for receiving the
barrel 20. The cap 40 is provided with an internal thread 43
matching the thread 23 of the barrel 20. Below the thread 43 of the
cap 40, as seen from the inlet end of the cap 40, and adjacent to
the open end of the cap (40) is a cylindrical flange 44 arranged,
which ends the cap 40 in the open end of the cap 40. The inner
diameter of the flange 44 is such that it can accommodate the
protrusion or protrusions 24 of the barrel 20 without contacting,
or just contacting, the protrusions 24, in order for providing a
smooth mounting of the cap 40 onto the barrel 20. A play between
the protrusion 24 and the inner surface 45 of the flange 44 up to
the order of a few millimetres may be acceptable. The flange (44)
has preferably a continuous surface, but may have cut outs.
Accommodated should be understood that each protrusion (24) is
covered by a flange portion.
The flange 44 of the cap 40 is provided with at least one
post-fabricated locking member 46 extending essentially radially
inwards from the inner cylindrical surface of the flange 44 of the
cap 40. According to one embodiment of the invention the locking
member 46 is an indent. The indent 46 extents a distance from the
inner surface 46 that substantially exceeds the play, if a play is
present. The overlap in the radial direction between the protrusion
24 and the indent 46 may preferably exceed at least a third of the
length that the protrusion 24 extends from the outer surface of the
barrel (20). As non-limiting examples: for a 200 g size cartridge
the indent 46 may be in the order of 2-5 mm and for smaller size
cartridges in the order of 1-3 mm. Alternatively one could describe
the relation between the protrusion 24 and indent 46 as overlapping
in the radial direction of the barrel 20, the overlap being in the
order of 1-5 mm.
The indent 46 should be positioned in relation to the protrusion 24
so that the indent 46 is after, and adjacent the protrusion 24 in
the screw direction. Preferably the indent 46 abuts the protrusion
24. This gives a secure locking of the cap 40, so it can not be
unscrewed from the barrel 20 and no play is present if a user is
trying to unscrew the cap 40 from the barrel 20. The position of
the indent 46 relative the protrusion 24 should further relate in
such a manner that it is in the fully closed position of the cap 40
that the indent 46 should lock the cap. Fully locked should here be
understood that the cap is screwed to a predetermined torque
providing a leak-proof enclosure.
The term "post-fabricated indent" is used to illustrate that the
locking member, for example the indent 46 has been provided in
connection with the final assembly of the pre-packed cartridge 10
and after the cap 40 has been screwed onto the barrel 20, it is not
a structure given by the moulding process, for example. The indent
24 have typically and preferably been provided to the flange by
punching the outer surface of the flange 44 with a punch with a
predetermined impact and punching depth in a last, or one of the
last steps in finalising the pre-packed cartridge 10. The punching
typically results in a local plastic deformation, i.e.
non-reversible deformation, of the flange 44. According to one
embodiment of invention the indent 46 comprises at least a portion
that is plastically deformed.
One purpose of the locking of the cap 40 is to ensure that the
cartridge is provided to an end user in an intact condition. This
includes hindering a user to unintentionally or purposely open the
cartridge. The locked cartridge should therefore withstand a
predetermined torque. The predetermined torque should relate to the
torque a human using her hands would exert on the cap-barrel,
taking into account parameters such as the dimension of the
cartridge. A typical torque asserted by a user can range from 3-10
Nm depending of the strength of the user, but also on the shape and
in particular, the size, of the cap. According to one embodiment of
the invention, the indent 46 and the protrusion 24 interact to
withstand a predetermined torque.
As described above the locking provided by the indent 46 and
protrusion 24 combination aims to prevent access to the interior of
the cartridge 10. However, in some circumstances it is preferred to
have access. After use the cartridges should normally be discarded.
However, modern re-cycling requirements typically require plastic
waste such as the cartridge to be separated from the chemical
infused materials from the interior. According to one embodiment of
the invention the indent 46 and the protrusion 24 interact to
withstand a first predetermined torque, but are arranged to break
at a second predetermined torque. The first predetermined torque
should relate to a torque typically achievable by human hands,
preventing a user to open the cartridge with her bare hands. The
second torque should be significantly higher than the first torque
but below a torque relating to the cap being opened with the aid of
a tool providing a lever or by a machine. Typically and preferably
the protrusion 24 has a higher stability than the indent 46,
causing the indent 46 to break or the flange 44 to flex outwards if
the second predetermined torque is exceeded. The possibility
provided by the invention of having a locking mechanism that
withstands all normal handling but breaks relatively easily
provided the correct opening equipment is used ensures an efficient
re-cycling of the cartridge. Applying the second torque should
preferably permanently deform the indent 46 and thereby prevent
unauthorised re-use of an opened cartridge.
According to one embodiment of the invention the barrel 20 and/or
the cap 40 are provided with respective alignment means 28, 48 for
facilitating a correct positioning of the punch that forms the
indent 46 in relation with the protrusion 24. The alignment means
28, 48 may be visual markings, ridges or knobs, for example.
Alternatively the barrel is provided with a support structure with
a second purpose of mounting the cartridge to the chromatograph,
which support structure in addition is used to position and
aligning the barrel 20 in the punching process. Accordingly only
the cap 40 needs alignment means 48, for example a visual mark or a
knob.
According to one embodiment of the invention the cartridges 20 is
provided with a plurality of protrusions 24 and indents 46,
arranged pairwise in close proximity to each other. Preferably the
number of protrusion/indent pairs is between 2 and 6, and even more
preferably 3 or 4. The number of protrusion/indent pairs affect the
force exerted on each pair of indent/protrusion if an opening
action is performed. The torque and the predetermined first and
second torque should be understood as the total torque to withstand
or break, respectively, exerted on the cap 40 relative the barrel
20. The skilled person would understand to adapt the design of each
pair of protrusion 24 and indent 46 with regards to the chosen
number of pairs, or visa versa, in order to adapt to the required
torque. The design parameters including, but not limited to: the
overlap of the protrusion 24 and indent 46 in the radial direction,
the protrusion/indent area and material properties of the
protrusion 24 and the indent 46.
The torque may be measured with a torque wrench. Alternatively the
torque T is established by measuring the force F acting
perpendicular on the Euclidean distance r from the rotation axis.
The torque is calculated as, .tau.=F.times.r (1)
In the work of establishing first and second predetermined torque,
the barrel 20 was fixed and a lever provided with a dynamometer was
attached to the cap 40. Table 1 lists torque needed to unscrew the
cap 40 from cartridges of different size. These values represent
appropriate second predetermined torques for respective sizes. If
compared to the torque range of 3-10 nm typical for a human using
her bare hands, it should be taken into account that for the small
size (5/10 g) it is the lower part of the range that is applicable
(around 3 nm), since the cap for such cartridge is small.
Preferably the second predetermined torque is 1.3 to 2 times higher
than the first predetermined torque. Manual tests with
representative test persons confirmed that the persons could not
open the cartridges with their hands.
TABLE-US-00001 TABLE 1 Torque for different cartridge size
Cartridge Torque (Nm) 200/340 g 18 50/100 g 11 5/10 g 8
The cartridge 10 has above been described with the cap 40 and
barrel 20 being joined with a thread. "Thread" should here be
interpret to include all types of joining mechanisms that utilizes
a twisting or screwing motion, for example bayonet couplings.
Having a cap on the inlet end and an integral end-piece on the
outlet end of the chromatography cartridge represents a common
version in flash chromatography. Other alternatives could be
envisaged, for example having caps in both ends of the barrel which
both utilizes the above described locking mechanism. Alternatively
a cap is provided only at the outlet end of the cartridge and
provided with the locking mechanism. The skilled person would,
given the teachings herein, know how to adapt the different parts
to function according to the present invention.
The protrusion 24 a hollow structure, for example of the form of a
cylinder and the indent 46 positioned so that it extends into the
hollow of the protrusion 24--The protrusion 24 may also be realized
as two ridges extending in a direction perpendicular to the screw
direction and the indent 46 extending in-between the two
ridges.
The method according to the invention of final assembling of a
closed chromatography cartridge with a punching machinery 30,
illustrated in the flowchart of FIG. 2 and in the drawings of FIGS.
3a-c, comprises the steps:
20: Providing a barrel packed with chromatography media, internal
support structures, frits etc.
22: Positioning the barrel in a punching equipment comprising at
least one punch 32 and aligning the protrusion 24 of the barrel 20
so that the punch 32 is positioned a predetermined distances after
the protrusion 24 in the screw direction. Positioning and aligning
may be done in a single action, for example using the alignment
means 28 of the barrel. Alternatively the barrel 20 is first placed
in a support 31 and sequentially aligned. 24: Applying the cap 40
to the top of the barrel 20. 26: Screwing the cap 40 with a
predetermined torque. If the barrel 20 has been correctly aligned
with regards to the punch 32, it is only necessary to ensure that
the cartridge 10 is properly closed, since the punches can be
placed anywhere on the flange 44 of the cap 40. Alternatively the
position is determined by aligning respective alignment means of
the cap 40 and the barrel 20 with each other. 27: Punching the
flange 44 of the cap 40 with a punch 32 to produce at least one
indent 46. The punch 32 is typically and preferably operated by a
pneumatic cylinder 33 that can be set to a predetermined punching
depth and/or punching force. As can be seen in the schematic
illustration of FIG. 3c the punch should hit the flange 44 of the
cap 40 so to produce an indent that abuts the protrusion 26. The
punch depth should be adjusted so that the punch never touches the
outer surface of the barrel 20. 28: In an optional step the
cartridge 10 is rotated a with regards to the punch 32 and the
punching step 27 is repeated. If more than two indents 46 are to be
provided the steps of punching 27 and rotating 28 are repeated.
The predetermined distance in positioning and alignment step 22
should be selected so that the punch 32 will cause an indent 46 of
the cap 40 that abuts the protrusion 24 of the barrel 20. Given
that requirement the skilled operator may with a limited test
series determine a suitable predetermined distance. Similarly, a
correct punch depth/force is preferably determined by testing.
According to one embodiment of invention the punch depth/force is
selected to give an indent 46 that is at least partly plastically
deformed.
According to one alternative embodiment the punching step 27 and
rotation step 28 is replaced with a single multiple punching step
29. The punching machinery is provided with plurality of punches 32
and respective pneumatic cylinders 33 each producing an indent 46
upon the punching operation. Preferably the punching of the
plurality of different punches is simultaneous in order to have a
balanced operation. Utilizing a plurality of punches saves time,
reduces the need to realign the cartridge between punches and the
lesser force exerted on the cartridge due to punch symmetry means
less risk of affecting the carefully packed media bed.
If the locking member is a melted structure the punching machinery
is replaced with equipment for localized melting, for example pin
or tap like resistive heaters or a laser heater. The requirements
and procedure regarding alignment will be the same.
Final assembling should here be understood as recognizing that a
number of manufacturing steps may have occurred before the
cartridge is packed with media and closed. Such manufacturing steps
include, but are not limited to, producing the barrel, cap and
internal structure and preparing the media. Depending on how the
manufacturing process is implemented, the final assembling may
comprise more, or fewer, steps than here described. The skilled
person would know how to adapt the method according to the
invention in order to comply with different manufacturing
processes.
The present invention is not limited to the above-described
embodiments. Various alternatives, modifications and equivalents
may be used. Therefore, the above embodiments should not be taken
as limiting the scope of the invention, which is defined by the
appending claims.
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